Studies were performed to elucidate the mechanism of cytotoxicity of AMSA (NSC-141549) and to determine the basis for selective toxicity exhibited by this agent in vivo. A rational approach to achieving selective toxicity was employed for AMSA against liver metastases and hepatocellular carcinoma utilizing detoxification mechanisms present in normal, fully differentiated liver cells but not present in certain tumors. In a continuing study, several additional bis-quinaldine derivatives were synthesized and their binding to DNA, inhibition of polymerizing enzymes, in vitro cytotoxicity and in vivo antitumor activity determined. The enzymatic activation of two new antitumor agents (3-deazauridine (NSC-126849) and aminothiadiazole (NSC-4728) was studied in normal and malignant cells. An assay was developed for quantitating the phosphorylation of 3-deazauridine in vitro and a comparison of its substrate activity with enzymes of various cells determined. In an attempt to elucidate the mechanism by which nicotinic acid reverses the toxic effects of aminothiadiazole a new rapid assay was developed for nicotinic acid phosphoribosyltransferase. However, aminothiodiazole was found not be a substrate for this activating enzyme. BIBLIOGRAPHIC REFERENCES: Sinha, B. K., Cysyk, R. L., Millar, D. B. and Chignell, C. F.: Synthesis and Biological Properties of Some Spin-Labeled 9-Aminoacridines. J. Med. Chem. 19: 994-998, 1976. Cysyk, R. L. and Adamson, R. H.: Protein Cross-Linking Properties of the Antitumor Agent Imosine Dialdehyde (NSC-118994). Cancer Treatment Rep. 60: 563-570, 1976.